Neural Circuit Of Sensory Cues Modulating Feeding Rate And Mechanism Of Temporal Fasting Modulating Fat Metabolism In C. Elegans

C. elegans as a model organism have many advantages, such as simple nervous system, convenient genetics and transparent body, these make them a good research model for neural circuit study and metabolism research. This thesis include two subjects:the first one is the chemicals modulating feeding rate and neural signals detection; the second is related to short time fasting modulating fat metabolism.Feeding is one of the most important behaviors of nature animals. Animals must face the complicated variations of their circumstances, these changes include physical and chemical factors. However, whether these changes could modulate the feeding behavior is not clear now. We choose C. elegance as a research model and choose Dactyls as an attractant,100% isoamylol and quinine as repellants. Mix them into the feeding circumstance of C. elegans, we found that attractant can increase the feeding rate, while repellants can decrease feeding rate. By screening the feeding modulation defect mutants, adding exogenous transmitters and measuring calcium, we demonstrated that chemicals modulate feeding rate via sensory system, and these modulations are based on a neural circuit comprising both pharyngeal nervous system and exo-pharyngeal nervous system, the pharyngeal serotoninergic neurons NSM and exo-pharyngeal tyraminergic/ octopaminergic neurons RIM/RIC and the inhibit tyramine receptor SER-2, serotonin gated Cl- channel MOD-1 make up a reciprocal inhibition circuit to modulate the feeding rate during chemicals exposure. This reciprocal inhibition circuit filter the environmental cues, enhancing some cues that are essential to animals and passing over others that are not essential, which ensure a stable behavior under a complicated environment.How to detect neural signals in a circuit is a foundational and important question in neural circuit research. Hitherto, the most common method to detect neural signals in C. elegans is calcium imaging, surprisingly, methods that to detect the direct signal carriers—the transmitters, haven't been developed. We employ amperometry to detect secretion of C. elegans serotoninergic neuron NSM, owing to their small size, traditionary big size electrodes are not available to detect secretion in NSM neurons, we developed a new strategy of chemical etch based on a micro-region electrolyte and got size-controllable, smooth face and well insulation carbon fiber electrodes. With these electrodes, we detected serotonin secretion from C. elegans NSM. Moreover, amperometry based on these electrodes became a powerful system to study mechanism of secretion in C. elegans.Abnormal fat storage is an important source of lysosome disorders, which do a great harm to human health. While, how lysosome participates in lipid metabolism is not very clear now. Owing to the convenient genetics and chemical screening, we choose C. elegans as a research model to study the relationship between lysosome and lipid metabolism. We used Nile Red to stain C. elegans fat, we observed that short time fasting induced a great increase of fed Nile Red fluorescence, subsequently, we found that the Nile Red staining fat was polar lipid in lysosome-related organelles(LRO) but not reported neutral lipid, nor lipofuscin. We found that this type of fat can be breakdown in LRO which further suggested that this was not stored fat. We also found that, during short fasting, PKG mediated a sensory signal to induce an accumulation of polar lipid in LRO, while NHR-49 mediated an inhibitory signal to control the accumulation by inhibiting polar lipid transporting into LRO and improving breakdown, these ways ensure a stable level of polar lipid in LRO under short time fasting.